Preparation method of 4-(heptafluoro-2-propyl)-2-trifluoromethylaniline and application thereof

Abstract

The present disclosure provides a preparation method of 4-(heptafluoro-2-propyl)-2-trifluoromethylaniline and an application thereof. The preparation method comprises the following steps: reacting 2-aminobenzotrifluoride and 2-bromoheptafluoropropane in the presence of sodium formate or hydrates thereof and a SO.sub.2 reagent, so as to obtain 4-(heptafluoro-2-propyl)-2-trifluoromethylaniline. The present disclosure adds sodium formate or hydrate thereof and the SO.sub.2 reagent during the reaction of 2-aminobenzotrifluoride and 2-bromoheptafluoropropane. Under the cooperation of these two compounds, the yield of the reaction is high. And the purity of the product is high, the operation method is simple, the cost is relatively low, and the pH of the reaction doesn't need to be controlled.

Claims

1. A preparation method of 4-(heptafluoro-2-propyl)-2-trifluoromethylaniline, comprising: reacting 2-aminobenzotrifluoride and 2-bromoheptafluoropropane in the presence of sodium formate or hydrates thereof and a SO.sub.2 reagent, so as to obtain 4-(heptafluoro-2-propyl)-2-trifluoromethylaniline.

2. The preparation method according to claim 1, wherein a molar ratio of sodium formate or hydrates thereof and 2-aminobenzotrifluoride is (0.1˜2):1.

3. The preparation method according to claim 1, wherein a molar ratio of the SO.sub.2 reagent and 2-aminobenzotrifluoride is (0.05˜2)1.

4. The preparation method according to claim 1, wherein a molar ratio of 2-bromoheptafluoropropane and 2-aminobenzotrifluoride is (1.0˜2):1.

5. The preparation method according to claim 1, wherein the SO.sub.2 reagent include any one or at least two combinations of sodium dithionite, SO.sub.2, alkali metal sulfite, alkali metal bisulfites, alkaline-earth metal sulfite, alkaline-earth metal bisulfites, (NH.sub.4).sub.2SO.sub.3 or NH.sub.4HSO.sub.3.

6. The preparation method according to claim 1, wherein the reaction system also includes a solvent, wherein the solvent includes any one of or at least two combinations of water, methyl acetate, ethyl acetate, propyl acetate, butyl acetate, isopropyl acetate, tert-butyl acetate, tert-butanol, acetonitrile, propionitrile, 1,4-dioxane, tetrahydrofuran, methyl tert-butyl ether, dichloromethane, 1,2-dichloroethane, trichloromethane, carbon tetrachloride, benzene, toluene or xylenes.

7. The preparation method according to claim 1, wherein the reaction system also includes a phase transfer catalyst, wherein the phase transfer catalyst includes tetrabutylammonium hydrogen sulfate.

8. The preparation method according to claim 1, wherein the reaction temperature is 5° C˜140° C., the reaction time is 2 h˜20 h, and the reaction is carried out at a pressure of 0˜10 MPa.

9. The preparation method according to claim 1, wherein noble gases are introduced into the reaction to improve the pressure of the reaction system.

10. The preparation method according to claim 1, wherein the preparation method comprises the following steps: (1) adding 2-aminobenzotrifluoride, a solvent with a mass ratio of (1˜8):1 to 2-aminobenzotrifluoride, sodium formate or hydrates thereof with a molar ratio of (0.1˜2):1 to 2-aminobenzotrifluoride, a SO.sub.2 reagent with a molar ratio of (0.05˜2):1to 2-aminobenzotrifluoride, and 2-bromoheptafluoropropane with a molar ratio of (0.05˜2)1 to 2-aminobenzotrifluoride to an autoclave, introducing noble gas into the reaction to obtain a 0˜10 MPa system pressure, heating the system to 5° C˜140° C., and reacting for 20 hours to obtain crude products; and (2) separating or filtering the crude product obtained by the step (1) to obtain an organic layer, and performing pressure-reduced distillation to the organic layer to remove the solvent, washing with sodium carbonate and water respectively, and then performing pressure-reduced distillation again to obtain 4-(heptafluoro-2-propyl)-2-trifluoromethylaniline.

Description

DETAILED DESCRIPTION

(1) Representative Examples of the present disclosure will be described in the following Examples. Those skilled in the art should understand that the examples herein are only illustrative, and the present disclosure is not limited thereto. The content (purity) or yield of the Examples and the present disclosure refers to a mass content (purity) or yield, which is not specifically described.

Example 1

(2) This example provides a method of preparing 4-(heptafluoro-2-propyl)-2-trifluoromethylaniline, and the specific operation is as follows.

(3) 2-aminobenzotrifluoride (82.2 g, 0.5 mol), water (164.4 g), acetonitrile (164.4 g), sodium formate (63 g, 0.6 mol), sodium hydrosulfite (19.8 g, 0.1 mol) and 2-bromoheptafluoropropane (149.4 g, 0.6 mol) was sequentially added to the 2 L autoclave, nitrogen was introduced to the reaction, and the pressure of the reaction system was 0.2 MPa. The mixture was then stirred at 40° C. for 18 h. After the reaction was completed, the liquid was separated, and acetonitrile was removed from the organic layer under reduced pressure. The residue was washed with 100 g of 10% sodium carbonate solution and 50 g of water to obtain a yellow oil. The crude product was distilled under reduced pressure (3 mmHg, 100° C.) to obtain the target compound (160.9 g). High pressure liquid chromatography external standard method is determined that the purity of the compound is 98.1%, yield 95.9%.

(4) Structural detection: Mass spectrometry: LC/MS[M+1]: m/z=330;

(5) .sup.1H NMR (400 MHz, DMSO-d.sub.6) (δ[ppm]): δ7.52 (d, J=8.9 Hz, 2H), 7.10 (d, J=8.6 Hz, 1H), 6.38 (s, 2H).

Example 2

(6) This example provides a method of preparing 4-(heptafluoro-2-propyl)-2-trifluoromethylaniline, and the specific operation is as follows.

(7) 2-aminobenzotrifluoride (82.2 g, 0.5 mol), water (164.4 g), ethyl acetate (246.6 g), tetrabutylammonium hydrogen sulfate (4.2 g), sodium formate (48.1 g, 0.7 mol), sodium hydrosulfite (69.3 g, 0.35 mol) and 2-bromoheptafluoropropane (199.2 g, 0.8 mol) was sequentially added to the 2 L autoclave, nitrogen was introduced to the reaction, and the pressure of the reaction system was 1.1 MPa. The mixture was then stirred at 60° C. for 14 h. After the reaction was completed, the liquid was separated, and ethyl acetate was removed from the organic layer under reduced pressure. The residue was washed with 100 g of 10% sodium carbonate solution and 50 g of water to obtain a yellow oil. The crude product was distilled under reduced pressure (3 mmHg, 100° C.) to obtain the target compound (162.1 g). High pressure liquid chromatography external standard method is determined that the purity of the compound is 97.9%, yield 96.4%.

(8) Structural detection: Mass spectrometry: LC/MS[M+1]: m/z=330.

Example 3

(9) This example provides a method of preparing 4-(heptafluoro-2-propyl)-2-trifluoromethylaniline, and the specific operation is as follows.

(10) 2-aminobenzotrifluoride (82.2 g, 0.5 mol), water (246.6 g), tert-butanol (246.6 g), sodium formate (84 g, 0.8 mol), sodium hydrosulfite (118.8 g, 0.6 mol) and 2-bromoheptafluoropropane (224.1 g, 0.9 mol) was sequentially added to the 2 L autoclave, nitrogen was introduced to the reaction, and the pressure of the reaction system was 2.0 MPa. The mixture was then stirred at 80° C. for 10 h. After the reaction was completed, the liquid was separated, and tert-butanol was removed from the organic layer under reduced pressure. The residue was washed with 100 g of 10% sodium carbonate solution and 50 g of water to obtain a yellow oil. The crude product was distilled under reduced pressure (3 mmHg, 100° C.) to obtain the target compound (164.1 g). High pressure liquid chromatography external standard method is determined that the purity of the compound is 97.5%, yield 97.2%.

(11) Structural detection: Mass spectrometry: LC/MS[M+1]: m/z=330.

Example 4

(12) This example provides a method of preparing 4-(heptafluoro-2-propyl)-2-trifluoromethylaniline, and the specific operation is as follows.

(13) 2-aminobenzotrifluoride (82.2 g, 0.5 mol), water (164.4 g), 1,2-dichloroethane (246.6 g), tetrabutylammonium hydrogen sulfate (4.2 g), sodium formate (84 g, 0.8 mol), sodium hydrosulfite (69.3 g, 0.35 mol) and 2-bromoheptafluoropropane (224.1 g, 0.9 mol) was sequentially added to the 2 L autoclave, nitrogen was introduced to the reaction, and the pressure of the reaction system was 1.1 MPa. The mixture was then stirred at 80° C. for 10 h. After the reaction was completed, the liquid was separated, and 1,2-dichloroethane was removed from the organic layer under reduced pressure. The residue was washed with 100 g of 10% sodium carbonate solution and 50 g of water to obtain a yellow oil. The crude product was distilled under reduced pressure (3 mmHg, 100° C.) to obtain the target compound (163.9 g). High pressure liquid chromatography external standard method is determined that the purity of the compound is 97.2%, yield 96.8%.

(14) Structural detection: Mass spectrometry: LC/MS[M+1]: m/z=330.

Example 5

(15) This example provides a method of preparing 4-(heptafluoro-2-propyl)-2-trifluoromethylaniline, and the specific operation is as follows.

(16) 2-aminobenzotrifluoride (82.2 g, 0.5 mol), acetonitrile (328.8 g), sodium formate (31.5 g, 0.3 mol), sodium hydrosulfite (19.8 g, 0.1 mol) and 2-bromoheptafluoropropane (149.4 g, 0.6 mol) was sequentially added to the 2 L autoclave, nitrogen was introduced to the reaction, and the pressure of the reaction system was 0.2 MPa. The mixture was then stirred at 70° C. for 18 h. After the reaction was completed, the reaction system was filtered, and acetonitrile was removed from the organic layer under reduced pressure. The residue was washed with 100 g of 10% sodium carbonate solution and 50 g of water to obtain a yellow oil. The crude product was distilled with reduced pressure (3 mmHg, 100° C.) to obtain the target compound (160.5 g). High pressure liquid chromatography external standard method is determined that the purity of the compound is 97.1%, yield 94.7%.

(17) Structural detection: Mass spectrometry: LC/MS[M+1]: m/z=330.

Example 6

(18) This example provides a method of preparing 4-(heptafluoro-2-propyl)-2-trifluoromethylaniline, and the specific operation is as follows.

(19) 2-aminobenzotrifluoride (82.2 g, 0.5 mol), acetonitrile (411 g), sodium formate (63 g, 0.6 mol), SO.sub.2 (12.8 g, 0.2 mol) and 2-bromoheptafluoropropane (174.3 g, 0.7 mol) was sequentially added to the 2 L autoclave, nitrogen was introduced to the reaction, and the pressure of the reaction system was 1.1 MPa. The mixture was then stirred at 90° C. for 16 h. After the reaction was completed, the reaction system was filtered, and acetonitrile was removed from the organic layer under reduced pressure. The residue was washed with 100 g of 10% sodium carbonate solution and 50 g of water to obtain a yellow oil. The crude product was distilled with reduced pressure (3 mmHg, 100° C.) to obtain the target compound (158.6 g). High pressure liquid chromatography external standard method is determined that the purity of the compound is 96.9%, yield 93.4%.

(20) Structural detection: Mass spectrometry: LC/MS[M+1]: m/z=330.

Example 7

(21) This example provides a method of preparing 4-(heptafluoro-2-propyl)-2-trifluoromethylaniline, and the specific operation is as follows.

(22) 2-aminobenzotrifluoride (82.2 g, 0.5 mol), 1,2-dichloroethane (493.2 g), sodium formate (52.0 g, 0.5 mol), Na.sub.2SO.sub.3 (30.9 g, 0.3 mol) and 2-bromoheptafluoropropane (224.1 g, 0.9 mol) was sequentially added to the 2 L autoclave, nitrogen was introduced to the reaction, and the pressure of the reaction system was 2.0 MPa. The mixture was then stirred at 110° C. for 14 h. After the reaction was completed, the reaction system was filtered, and 1,2-dichloroethane was removed from the organic layer under reduced pressure. The residue was washed with 100 g of 10% sodium carbonate solution and 50 g of water to obtain a yellow oil. The crude product was distilled with reduced pressure (3 mmHg, 100° C.) to obtain the target compound (159.3 g). High pressure liquid chromatography external standard method is determined that the purity of the compound is 97.0%, yield 93.9%.

(23) Structural detection: Mass spectrometry: LC/MS[M+1]: m/z=330.

Example 8

(24) This example provides a method of preparing 4-(heptafluoro-2-propyl)-2-trifluoromethylaniline, and the specific operation is as follows.

(25) 2-aminobenzotrifluoride (82.2 g, 0.5 mol), acetonitrile (328.8 g), sodium formate (52.0 g, 0.5 mol), NaHSO.sub.3 (31.2 g, 0.3 mol) and 2-bromoheptafluoropropane (224.1 g, 0.9 mol) was sequentially added to the 2 L autoclave, nitrogen was introduced to the reaction, and the pressure of the reaction system was 1.1 MPa. The mixture was then stirred at 110° C. for 14 h. After the reaction was completed, the reaction system was filtered, and 1,2-dichloroethane was removed from the organic layer under reduced pressure. The residue was washed with 100 g of 10% sodium carbonate solution and 50 g of water to give a yellow oil. The crude product was distilled with reduced pressure (3 mmHg, 100° C.) to obtain the target compound (159.3 g). High pressure liquid chromatography external standard method is determined that the purity of the compound is 97.3%, yield 94.2%.

(26) Structural detection: Mass spectrometry: LC/MS[M+1]: m/z=330.

Example 9

(27) This example provides a method of preparing 4-(heptafluoro-2-propyl)-2-trifluoromethylaniline, and the specific operation is as follows.

(28) 2-aminobenzotrifluoride (82.2 g, 0.5 mol), water (164.4 g), acetonitrile (164.4 g), sodium formate (5.25 g, 0.05 mol), sodium hydrosulfite (19.8 g, 0.1 mol) and 2-bromoheptafluoropropane (149.4 g, 0.6 mol) was sequentially added to the 2 L autoclave, nitrogen was introduced to the reaction, and the pressure of the reaction system was 0.2 MPa. The mixture was then stirred at 40° C. for 18 h. After the reaction was completed, the liquid was separated, and acetonitrile was removed from the organic layer under reduced pressure. The residue was washed with 100 g of 10% sodium carbonate solution and 50 g of water to obtain a yellow oil. The crude product was distilled with reduced pressure (3 mmHg, 100° C.) to obtain the target compound (125.9 g). High pressure liquid chromatography external standard method is determined that the purity of the compound is 99.1%, yield 75.8%.

(29) Structural detection: Mass spectrometry: LC/MS[M+1]: m/z=330.

Example 10

(30) This example provides a method of preparing 4-(heptafluoro-2-propyl)-2-trifluoromethylaniline, and the specific operation is as follows.

(31) 2-aminobenzotrifluoride (82.2 g, 0.5 mol), water (164.4 g), ethyl acetate (164.4 g), sodium formate (15.75 g, 0.15 mol), sodium hydrosulfite (19.8 g, 0.1 mol) and 2-bromoheptafluoropropane (149.4 g, 0.6 mol) was sequentially added to the 2 L autoclave, nitrogen was introduced to the reaction, and the pressure of the reaction system was 0.2 MPa. The mixture was then stirred at 40° C. for 14 h. After the reaction was completed, the liquid was separated, and ethyl acetate was removed from the organic layer under reduced pressure. The residue was washed with 100 g of 10% sodium carbonate solution and 50 g of water to obtain a yellow oil. The crude product was distilled with reduced pressure (3 mmHg, 100° C.) to obtain the target compound (132.7 g). High pressure liquid chromatography external standard method is determined that the purity of the compound is 99.2%, yield 80.0%.

(32) Structural detection: Mass spectrometry: LC/MS[M+1]: m/z=330.

Example 11

(33) This example provides a method of preparing 4-(heptafluoro-2-propyl)-2-trifluoromethylaniline, and the specific operation is as follows.

(34) 2-aminobenzotrifluoride (82.2 g, 0.5 mol), water (164.4 g), tert-butanol (164.4 g), sodium formate (26.25 g, 0.25 mol), sodium hydrosulfite (19.8 g, 0.1 mol) and 2-bromoheptafluoropropane (149.4 g, 0.6 mol) was sequentially added to the 2 L autoclave, nitrogen was introduced to the reaction, and the pressure of the reaction system was 0.2 MPa. The mixture was then stirred at 40° C. for 10 h. After the reaction was completed, the liquid was separated, and tert-butanol was removed from the organic layer under reduced pressure. The residue was washed with 100 g of 10% sodium carbonate solution and 50 g of water to obtain a yellow oil. The crude product was distilled with reduced pressure (3 mmHg, 100° C.) to obtain the target compound (142.1 g). High pressure liquid chromatography external standard method is determined that the purity of the compound is 99.1%, yield 85.6%.

(35) Structural detection: Mass spectrometry: LC/MS[M+1]: m/z=330.

Example 12

(36) This example provides a method of preparing 4-(heptafluoro-2-propyl)-2-trifluoromethylaniline, and the specific operation is as follows.

(37) 2-aminobenzotrifluoride (82.2 g, 0.5 mol), acetonitrile (328.8 g), sodium formate (104.0 g, 1.0 mol), NaHSO.sub.3 (31.2 g, 0.3 mol) and 2-bromoheptafluoropropane (224.1 g, 0.9 mol) was sequentially added to the 2 L autoclave, nitrogen was introduced to the reaction, and the pressure of the reaction system was 1.1 MPa. The mixture was then stirred at 110° C. for 10 h. After the reaction was completed, the liquid was separated, and tert-butanol was removed from the organic layer under reduced pressure. The residue was washed with 100 g of 10% sodium carbonate solution and 50 g of water to obtain a yellow oil. The crude product was distilled with reduced pressure (3 mmHg, 100° C.) to obtain the target compound (156.2 g). High pressure liquid chromatography external standard method is determined that the purity of the compound is 97.0%, yield 92.1%.

(38) Structural detection: Mass spectrometry: LC/MS[M+1]: m/z=330.

Comparative Example 1

(39) The difference from Example 1 is that sodium formate is replaced with the same amount of substance sodium carbonate. Liquid separation after reaction, high pressure liquid chromatography external standard method is determined that the yield of the target compound is 61.3%.

(40) Structural detection: Mass spectrometry: LC/MS[M+1]: m/z=330.

(41) The above results demonstrate that the preparation method provided by the present disclosure has a high yield. The yield is higher than 93%, up to 97%.

(42) Comparative example 1 only replaced sodium dihydrate with sodium carbonate, and the yield of the reaction is significantly reduced. This proves that the addition of sodium dihydrate in the present disclosure plays a crucial effect on the increase of yields.

(43) The present disclosure illustrates the detailed method of the present disclosure by the above examples. However, the present disclosure is not limited to the above detailed method. It does not mean that the present disclosure must rely on the above detailed method to implement. Those skilled in the art should understand that any improvements of the disclosure (equivalent replacement of all raw materials of the products of the present disclosure, addition of auxiliary components, or the selection of specific methods, etc.) are within the scope of the disclosure.